Hsa-miR-342-3p and hsa-miR-360 may be the key molecules that promote periodontitis in type 2 diabetes mellitus

Abstract

Background: Periodontitis (PD) has been acknowledged as a complication associated with type 2 diabetes mellitus (T2DM). However, the precise mechanism through which T2DM fosters the development of PD remains elusive. Our objective is to elucidate the connection between these two conditions by conducting bioinformatics analysis. Methods: In this study, we analyzed miRNA datasets pertaining to T2DM and PD sourced from GEO. Through differential expression analysis, we identified common differentially expressed miRNAs (DE-miRNAs) and subsequently analyzed the functional enrichment of these common DE-miRNAs. We further leveraged the PD transcriptome database to select DE-miRNA-targeted mRNAs and examined their association with immune infiltration. Finally, machine learning was used to further screen hub DE-miRNA-targeted mRNAs and validate our data in external datasets. Results: Two common DE-miRNAs, namely hsa-miR-342-3p and hsa-miR-360, were identified from the miRNA datasets of PD and T2DM. Functional enrichment analysis indicated that these two common DE-miRNAs predominantly participate in Ras, PI3K-Akt, p53, and MAPK signaling pathways. Integration of the PD transcriptome dataset revealed a total of 21 DE-miRNA-targeted mRNAs in PD, with strong correlations observed with plasma cells and dendritic cells. Finally, three hub DE-miRNA-targeted mRNAs (hsa-miR-342-3p-/hsa-miR-360-RASAL2, hsa-miR-360-ENTPD1/PLXDC2) were identified. ENTPD1 exhibited a robust positive correlation with plasma cells and a negative correlation with resting dendritic cells. Conclusions: Therefore, hsa-miR-342-3p-/hsa-miR-360-RASAL2, as well as hsa-miR-360-ENTPD1/PLXDC2, may serve as diagnostic and therapeutic targets for T2DM-associated PD.

Keywords

• Periodontitis
• Type 2 diabetes mellitus
• miRNA
• Immune infiltration
• Ras signaling pathway